The 21-year-old edged out Duncan Scott in one minute 45.55 seconds to add to his 100m, 200m and 400m butterfly wins.
"I really wanted that one," Guy said. "It's kind of my event."
Sarah Vasey, 20, won the 100m breaststroke in a new personal best time of 1:06.78.
Ben Proud, 22, set a British record of 22.80 seconds in the 50m butterfly having also broken a record in the 50m freestyle on Saturday.
Alys Thomas, 26, took gold in the women's 100m butterfly while Luke Greenbank, 19, triumphed in the 200m backstroke.
Double Olympic silver medallist James Guy secured his fourth gold medal of the British Swimming Championships with victory in the 200m freestyle on the final day.