Rose bogeyed three holes – 12, 14, and 16 – to give him too much to do as he shared fourth on 17 under at the DP World Tour Championship in Dubai despite leading the field after the third round.
Fleetwood, who also struggled in his final round, shooting a two over 74, finished down in joint 21st.
But the 26-year-old from Southport had done enough to secure the No.1 spot on the European Tour as Jon Rahm won the final event in Dubai.
Fleetwood shot 73, 65, 65, and 72 but his two wins on the Tour this season were enough to top the pile.
He won with a final score of 5,420,530 points to Rose’s 4,921,062 to Rose’s after victories at the HNA Open de France and the Abu Dhabi HSBC Championship.
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Rose, who came back into contention with back-to-back wins in Turkey and China, had a mixed final event with rounds of 66, 70, 65 and then the one under 70 to finish.
Fleetwood was in the clubhouse with his fiance and young child with Rose needing an eagle on the par 5 18th.
But his drive hit the rough and second shot gave him too much to do – finishing with a birdie but only managing a joint fourth place.
An emotional Fleetwood said on Sky Sports: “It wasn’t pretty today, most of the time, but it was great being out there to try and win it.
“Trying to win the tournament first and the actually come here today trying to win the Race to Dubai and it’s all worked out.
“It’s a funny old game, from where I started the day, two great shots down one and I knocked it in and then struggling getting things going.
“I made some great pars on 15 and 16 and it’s always difficult because it really was out of my control and down the last few holes I just had to keep it in and try and do the best I could.
“You want the grand stand finish, you want to do something amazing to win it but it doesn’t always work out that way and a year’s graft has come down to this.”
Rahm, 23, who only turned professional in June last year, finished a shot ahead of Thailand’s Kiradech Aphibarnrat and Ireland’s Shane Lowry, whose 63 equalled the lowest round of the week.
Masters champion Sergio Garcia and the South Africa duo of Dean Burmester and Dylan Frittelli were alongside Olympic champion Rose.