Hatters defender Luke Wilkinson headed home the opening goal after 80 seconds to gift Luton a promising start.
Pelly Ruddock Mpanzu came close to doubling the hosts' lead a minute after Wilkinson's goal, but his shot went just past the post.
Luton went into the break with the lead, as Oxford failed to threaten despite carving out a couple of promising openings.
The penalty was initially saved but Howells followed up to score off the rebound.
Oxford began to search for the goal to get them back into the game but ultimately ran out of time as the match ended 2-0 to the hosts.