The high-school band The Paragons evolved into Dynasty before Thompson formed Mandrake, a group that played weekend dances in Hamilton. Then in 1972, he returned to England via Australia.

Thompson joined Manfred Mann's Earth Band as vocalist and sang on the 1976 worldwide hit 'Blinded By the Light', the band's cover of a Bruce Springsteen song. He recorded and toured with the Earth Band from 1974 to 1999 but also released his own solo albums and two albums with his own band Night. In 1978, he was featured on Jeff Wayne's War of the World recording, singing the lead vocal on 'Thunder Child'.

Thompson's next band Night grew out of his London pub band, Filthy McNasty, featuring Stevie Lange (female vocalist), Robbie McIntosh (guitar) and Billy Kristian (bass). Piano legend Nicky Hopkins (The Beatles, The Rolling Stones) was also added to the Night line-up. The band recorded two albums with famed Los Angeles record producer Richard Perry for his Planet record label. The self-titled 1979 album had two US Top 40 hits, 'Hot Summer Nights' (No.18) and 'If You Remember Me' (No.17). 'Hot Summer Nights' was a cover of a Walter Egan song and it went to No.3 on the Australian sales charts and No.28 in New Zealand. The album only achieved No.113 on the US sales charts. The second Night album Long Distance, released in 1980, was less successful.

Chris Thompson said to Rip It Up  in July 1984, “My career has been a nightmare – not in the sense that I can never get anything happening, but in that I can never get any unification of thrust in any direction.”

In 1986, Thompson had massive success as a co-writer of the John Farnham hit 'You're The Voice'.

In 1986, Thompson had massive success co-writing 'You're The Voice', which propelled John Farnham's album Whispering Jack to become Australia's biggest selling album ever, with sales in excess of one and a half million units. The co-writers of the song were Andy Qunta (Icehouse), Keith Reid (Procol Harum lyricist) and Maggie Ryder (singer). After his demo had been rejected by record companies in London, Thompson gave the song to John Farnham.

Thompson fronted a band of top New Zealand musicians to sing 'This is the Moment' at the 1990 Commonwealth Games in Auckland. Playing with him were Mike Farrell (guitar), Lance Sua (guitar), Billy Karaitiana (formerly known as Billy Kristian, bass), Frank Gibson Jr (drums), Ben Gilgen (keyboards), Liam Ryan (keyboards). The backing vocalists were Peter Morgan, Kim Willoughby and Debbie Harwood.

In 1992 Chris worked with Queen band members to prepare for the Freddie Mercury tribute concert at Wembley Stadium, London. He also worked with Brian May and Roger Taylor on the 2003 Nelson Mandela 46664 Concert in Cape Town, South Africa. Thompson rehearsed the band and the Soweto Gospel Choir. At the concert Thompson sang 'The Show Must Go On' with Queen.

In 2005 Thompson performed with Manfred Mann on the Night Of The Proms tour, selling out 22 concerts in Germany. Between 2004 and 2010 Thompson also toured with Jeff Wayne’s The War Of The Worlds in Europe, Australia and New Zealand.

In 2012 Chris Thompson released an album performing standards with a big band and orchestra entitled Do Nothing Till You Hear From Me.