In 1960, Kristofferson graduated with a master's degree in English literature and married an old girlfriend, Fran Beir. He joined the United States Army and became a helicopter pilot. During the early 1960s, he was stationed in West Germany and returned to music and forming a band. Kristofferson sent some of his compositions to a friend's relative, Marijohn Wilkin, a successful Nashville, Tennessee songwriter. Kristofferson moved to Nashville after resigning his commission in 1965, intent on becoming a professional songwriter. He worked a variety of odd jobs while struggling to make it in the music business, burdened with expensive medical bills as a result of his son's defective esophagus. He and his wife soon divorced. In 1966, Dave Dudley released a successful Kristofferson single, "Viet Nam Blues". The following year, Kristofferson signed to Epic Records and released a single, "Golden Idol"/"Killing Time", but the song was not successful. Within the next few years, more Kristofferson originals hit the charts, performed by Roy Drusky ("Jody and the Kid"), Billy Walker & the Tennessee Walkers ("From the Bottle to the Bottom"), Ray Stevens ("Sunday Mornin' Comin' Down"), Jerry Lee Lewis ("Once More with Feeling") Faron Young ("Your Time's Comin'") and Roger Miller ("Me and Bobby McGee", "Best of all Possible Worlds", "Darby's Castle"). He also gained some success as a performer himself, due to Johnny Cash's introduction of Kristofferson at the Newport Folk Festival.
Kristofferson signed to Monument Records as a recording artist. The label was run by Fred Foster, also manager of Columbine Music, Kristofferson's songwriting label. His debut album for Monument was Kristofferson, which included a few new songs as well as many of his previous hits. Sales were poor. In spite of his failure as a recording artist, Kristofferson's compositions were still in high demand. Ray Price ("For the Good Times"), Waylon Jennings ("The Taker"), Bobby Bare ("Come Sundown"), Johnny Cash ("Sunday Morning Coming Down") and Sammi Smith ("Help Me Make It Through the Night") all recorded successful versions of his songs in the early 1970s. "For the Good Times" (Ray Price) won 'Song of the Year" in 1970 from the Academy of Country Music, while "Sunday Morning Coming Down" (Johnny Cash) won the same award from the Academy's rival, the Country Music Association in the same year. This is the only time an individual has won the same award from these two organizations in the same year for different songs.
In 1971, Janis Joplin, a very influential vocalist, had a #1 pop hit with "Me and Bobby McGee" off her posthumous Pearl, which was followed by more hits from Ray Price ("I Won't Mention It Again", "I'd Rather Be Sorry"), Joe Simon ("Help Me Make It Through the Night"), Bobby Bare ("Please Don't Tell Me How the Story Ends"), O.C. Smith ("Help Me Make It Through the Night") Jerry Lee Lewis ("Me and Bobby McGee"), Patti Page ("I'd Rather Be Sorry") and Peggy Little ("I've Got to Have You"). Kristofferson released his second album, The Silver Tongued Devil and I in 1971; the album was a success and established Kristofferson's career as a recording artist in his own right. Not long after, Kristofferson made his acting debut in The Last Movie (directed by Dennis Hopper) and appeared at the Isle of Wight Festival. In 1972, he acted in Cisco Pike and released his third album, Border Lord; the album was all-new material and sales were sluggish. He also swept the Grammies that year with numerous songs nominated and several winning song of the year. Kristofferson's 1972 fourth album, Jesus Was a Capricorn began slow but the third single, "Why Me", was a success and significantly increased album sales.
For the next few years, Kristofferson focused on acting. He appeared in Blume in Love (directed by Paul Mazursky) and Pat Garrett and Billy the Kid (directed by Sam Peckinpah) and also married Rita Coolidge. With his new wife, Kristofferson released an album called Full Moon, another success buoyed by numerous hit singles and Grammy nominations. However, his fifth album, Spooky Lady's Sideshow was a commercial failure, setting the trend for most of the rest of his career. Artists like Ronnie Milsap and Johnny Duncan continued to record Kristofferson's material with much success, but his own rough voice and anti-pop sound kept his own audience to a minimum. He continued acting, in Bring Me the Head of Alfredo Garcia, Alice Doesn't Live Here Anymore, Vigilante Force, The Sailor Who Fell from Grace with the Sea, and A Star Is Born (with Barbra Streisand). In spite of his success with Streisand, Kristofferson's career was heading downward with the non-charting ninth album, Shake Hands with the Devil. His next film, Freedom Road, did not earn a theatrical release in the US and he divorced Rita Coolidge. Meanwhile, more artists were taking his songs to the top of the charts, including Lena Martell ("One Day at a Time") and Willie Nelson, whose Willie Nelson Sings Kris Kristofferson LP was a smash success. Kristofferson's next film was Heaven's Gate, a phenomenal failure that temporarily ended his acting career.
In 1982, Kristofferson participated (with Willie Nelson, Dolly Parton and Brenda Lee) on The Winning Hand, a country success that failed to break into mainstream audiences. He then married again, to Lisa Meyers, and concentrated on films for a time, appearing in The Lost Honor of Kathryn Beck, Flashpoint and Songwriter. The latter also starred Willie Nelson and Kristofferson was nominated for an Academy Award for Best Original Song Score. Music from Songwriter (an album of duets between Nelson and Kristofferson) was a massive country success. Nelson and Kristofferson continued their partnership, and added Waylon Jennings and Johnny Cash to record Highwaymen. The album was a huge success, and the supergroup continued working together for a time. In 1985, Kristoferson starred in Trouble in Mind and released Repossessed a politically aware album that was a country success, particularly "They Killed Him" (also performed by Bob Dylan), a tribute to his heroes, including Martin Luther King Jr., Jesus Christ and Mohandas Gandhi. Kristofferson also appeared in Amerika at about the same time; the mini-series was controversial, hypothesizing life under Communist domination. In spite of the success with Highwaymen 2 in 1990, Kristofferson's solo recording career slipped significantly in the early 1990s, though he continued to successfully recorded with the Highwaymen. Lone Star (1996 film) reinvigorated Kristofferson's acting career, and he soon appeared in Blade, A Soldier's Daughter Never Cries, Fire Down Below and Payback (movie).