Half-back Brough, 38, played over 500 competitive games in a career that began at hometown club Dewsbury in 2002 and was named Man of Steel in 2013.
He captained Scotland in the World Cups of 2008, 2013 and 2017 and made a solitary appearance for England against the Exiles in 2012.
He spent most of his career in Super League with Wakefield, who he had three spells with, Huddersfield, where he was a driving force behind their 2013 League Leaders’ Shield triumph and Hull, with whom he won the 2005 Challenge Cup.
Brough joined Bradford in 2020 and in his last match, a Championship play-off tie semi-final at Batley in September, he kicked a goal to bring up 3,985 points and draw level with former Leigh stand-off John Woods in fifth place in the all-time scoring list.
Bradford coach John Kear, who also coached Brough at both Hull and Wakefield, said: “It is very sad news.
“It was the third time we have worked together and unfortunately it has come to a sad end but one I feel that Danny’s body was telling him and consequently I feel he has made the correct decision.
“A fit Danny Brough would get into any team but father time catches up with everyone and your body tells you when it is time.
“Danny has listened and hopefully he can enjoy a very illustrious retirement and reflect on everything he has achieved.
“He ends as the joint fifth highest points scorer in rugby league history and that is something to be very, very proud of.
“The number of appearances he has made is something to be very proud of. He has been involved in a League Leaders’ success, that is something to be very proud of and he has also won a Challenge Cup which is something to be very proud of.
“We would like to thank him for what he has done. We did not get to see the best of Danny which is unfortunate and the reasons for that are well documented in forcing his retirement on medical grounds but I would personally like to say thank you.
“I am sure the club would like to as well, I am sure Bradford fans and rugby league fans in general will wish Danny well and hope he has an illustrious future in front of him.”