His 1982 album Night Nurse, recorded at Bob Marley’s Tuff Gong studio, reached number 32 in the UK.
A cover version of the album’s title track, by Sly and Robbie featuring Simply Red, reached number 13 in the UK in September 1997.
Isaacs, who was diagnosed with lung cancer a year ago, had been travelling around Jamaica before returning home to London this summer to spend time with his wife, Linda, and his family.
"Gregory was well-loved by everyone, his fans and his family, and he worked really hard to make sure he delivered the music they loved and enjoyed," his wife said.
"He will be greatly missed by his family and friends."
Singer Suggs, speaking at the Q Awards in London, paid tribute to Isaacs, who supported his band Madness in concert.
"He was a great reggae artist and also one of the most sartorially elegant stars on the world stage," he said.
BBC News website readers have been sharing their memories:
I opened up for him in Hawaii with our then-group Tony Gits and the Lions Crew. It was his first US performance in some years and the island swelled for his music for it was what we all surfed to and loved. Upon his arrival to the islands and finding how much his music was loved, he was shocked into tears. He will be greatly missed. RIP Gregory. Peace. Keno Mapp, San Francisco, California, US
One of the most talented reggae artists in history, greatly under appreciated. A true crooner. My personal favourite is Reform Institution, although the bittersweet ballad Love Is Overdue and Universal Tribulation are true reggae classics. Pawel Krug, Amsterdam, The Netherlands
The music lives on. Gregory Isaacs has left a wonderful legacy in his numerous albums and dubs of his songs. I always enjoy hearing his tunes, as well as those of the late Sugar Minot, on the radio once or twice a week. I’m lucky to live near St Louis, Missouri, which has a great community radio station with two reggae shows. Both shows come on the air at that perfect time of the night for relaxation. There is so much more than Night Nurse in Isaacs’ back catalogue. Dig in and enjoy. Joe, Belleville, Illinois, US
Simply a great musician. I grew up listening to the "cool ruler" – everything about Gregory was smooth. Really huge loss to the reggae movement, but enough good tunes to remember forever. RIP. Mel Desouza, Surrey, UK
A stylish performer, cool and still the lad, Gregory Isaacs has left the stage for the last time. His material seems to have been a backing track for life in Hackney in the mid-80s. However, I saw him in Middlesbrough in 2008. What a memorable night! It’s sad that there are so few left of his genre – at least those who will perform for us in the North. Denise Robson, Gateshead, UK
I have been a life-long Gregory Isaacs fan. I grew up outside of Croydon and mixed with a Jamaican friend who introduced me to roots reggae, which has been a love ever since. I first heard a Gregory white label called It’s Too Late, which I managed to get on 12 inch. I have a lot of Gregory Jamaican import albums, but without question, the song which immortalised Gregory’s material was Soon Forward. Tony, from Peckham, UK,