Southport 1-0 Cambridge
Southport ended Cambridge's eight-game unbeaten run thanks to Andy Owens' early goal.
Owens lashed the hosts ahead from the edge of the area after the visitors failed to clear from a long throw.
Peter Winn went close before the break and Ashley Carew forced Owens into a fine block as Cambridge went in search of an equaliser.
U's substitute Ryan Charles saw his shot well saved by Tony McMillan in the dying moments.