Starting with Jake Livermore in midfield and new Liverpool signing Alex Oxlade-Chamberlain out wide, England struggled to find a way past an organised and combative Maltese side in the first-half.
The top scorer for the past two seasons in the Premier League collected a short pass from club teammate Dele Alli in the area and slotted home a finish from 10 meters in the 53rd minute, for his ninth global goal in 20 appearances.
The game went into its final 5 regulation minutes, where the Brit began to score more goals.
England are now 2 points ahead of Slovakia as they prepare to meet at Wembley Stadium on Monday.
The visitors kept with within two points of the Group F leaders thanks to a scruffy own goal that sank Slovenia 1-0 and will bid for a second victory over the weekend to actually overhaul England at the top of the standings.
After breaking a 12-game drought in style with a brace on Friday, England and Tottenham Hotspur forward Harry Kane chose to see the amusing side of his "August curse" with a light-hearted tweet. Raheem Sterling started there, Danny Welbeck was given the last 15 minutes out there (probably his best position) while Jesse Lingard and Jamie Vardy provide further options.
For Kane, the game offered a similar feeling to many of England's qualifying games in recent years, with the opposition happy to sit in and force their guests to break the deadlock. Kane was next to threaten but the Tottenham striker's header was well parried away by Hogg.
Southgate reacted to a tepid first-half performance by introducing Marcus Rashford, the forward replacing the ineffective Sterling on the left flank.
It was all a bit staccato from England for 85-odd minutes in Malta on Friday night but Gareth Southgate's troops stuck at it and the stoic hosts eventually ran out of puff. Their two point advantage over Slovakia is a touch precarious as a win for the visitors would raise the prospect of Southgate's side being forced into a play-off to reach Russian Federation 2018.
But England boss Gareth Southgate mentioned 34-year-old Defoe with regard to experienced members who could help nurture some of the youngsters in Rooney's absence.
Including the Hampden stalemate, England have won just one of their last five matches.
- Dele Alli has been involved in just two goals in his last 10 global appearances, however both have come against Malta (one goal, one assist).