Henderson won the 50m (38.50sec) and 200m (3min 02.04sec) breaststroke in the boys aged-11 grade.
His highlight was breaking the oldest long-course record on the Swimming Otago books in the 200m breaststroke.
He beat the record Jeff Conroy (Dunedin) set in February in 1971, also breaking his own record in the 50m breaststroke.
The event is the old teleprinter championships, with other meetings held in Auckland and Wellington.
The results from each venue are emailed to a central desk and the medallists worked out by computer by time.
Otago swimmers won five medals: three gold, one silver and one bronze.
Henderson, who is a member of coach Tim Holden's squad, has lowered his 200m time by 13sec over the past four months.
His time at Invercargill was two seconds faster than the next best swimmer in the country in his age group.
He also won a bronze medal in the 100m breaststroke, despite pulling a quadriceps muscle.
Hopkins swam a personal best time of 2min 28.46sec to win the gold medal in the boys aged-10 200m freestyle.
He also won a silver medal in the 100m freestyle with his time of 1min 10.63sec.
The other Otago medal at the championships came from Isobel Ryan (Oamaru), who won a bronze medal in the girls aged-12 50m backstroke in 33.24sec.
It was a top performance by the North Otago swimmers, with the Oamaru club being ranked second in the South Island behind Aqua Gym (Christchurch).
Aleisha Ruske (Neptune), who is coached by Punch Tremaine, broke a 15-year-old Otago record when she finished fifth in the girls aged-11 50m butterfly in 33.58sec.
It beat the record set by Hannah Shanks in 1994.
Ruske was fourth in the 100m butterfly in 1min 18.36sec.
Meanwhile, top Otago swimmer Bryn Murphy has shelved thoughts of retirement and is back in the water and will concentrate on ocean swimming for the London Olympic Games in 2012.
Murphy (22), who started a job with the Inland Revenue Department in Dunedin last November, decided to retire from competitive pool swimming after 13 years.
The freestyle specialist narrowly missed selection for the Beijing Games in his favoured 1500m, and he felt selection standards for the Commonwealth Games in New Delhi in 2010 and London would be too tough.
But after three months' rest he was persuaded to return to the water by coach Andy Adair and he showed he had not lost any fitness by convincingly winning the 2.8km ocean swim at Corsair Bay in Lyttelton Harbour in 37.07sec.
This swim was the third in the five-event national open-water series.
The remaining events are at Mt Maunganui and the North Shore in Auckland.
Adair is adding ocean swimming to the repertoire of his distance swimmers in the Waves squad.
Adam Simpson (16) finished second to Murphy in a time of 37min 38sec and Shane Patience was fourth in 38min 24sec.
In the women's 2.8km swim Phoebe Williams was third in 41min 32sec and Kate Medder (18) sixth in 42min 39sec.
In the open women's 750m race Stef Gillespie (13) was first in 10min 12sec, and Jordyn Fogarty won the 15-and-under age group in the 2.8km race in 43min 11sec.
