Calcavecchia had a 20-foot bogey save on the par-3 16th and parred the final two holes for a 2-under 70 and a 2-stroke victory over Langer on The Old Course at Broken Sound.
Langer also shot 70. Tied for the lead after Calcavecchia's bogey on 16, Langer fell back on the par-4 17th when he left a 4-foot par putt to the right. The German star also bogeyed the par-5 18th, driving to the right into pine straw and wood chips and finding two bunkers before reaching the green.
The 57-year-old Calcavecchia finished at 16-under 200. He opened with a 64 for a 1-stroke lead and birdied the final three Saturday in a 66 that left him two shots clear of Langer.
Calcavecchia won his fourth senior title and first since 2015. He won the 1989 British Open for one of his 13 PGA Tour titles.
The 60-year-old Langer won his home event in 2010. He won seven times last season, three of the victories in majors.
Charlie Rymer finished last in his senior debut, following rounds of 76 and 77 with an 87.