Ugandans taking part in an anti-gay demonstration in Kampala 2010.
A witnesses said David Kato was attacked at his home by a man who hit him over the head and then drove off in a vehicle.
Last year, under the headline “Hang Them”, his picture was printed on the front page of the Ugandan Rolling Stone newspaper as part of its campaign against homosexuality.
The paper, unconnected with the US magazine of the same name, published the names and photographs of what it described as “Uganda’s 100 top homos” and called for them to be executed.
David Kato, the advocacy officer for Uganda’s Organization of Sexual Minorities (SMUG), reportedly later received death threats.
“David Kato’s death is a tragic loss to the human rights community,” Maria Burnett of Human Rights Watch said.
“David faced the increased threats to the Ugandan LGBT people bravely and will be sorely missed,” Ms Burnett added.
The editor of the Rolling Stone, Giles Muhame, said that he condemned Mr Kato’s murder and insisted that his publication had not called for gays to be harmed.
“We want the government to hang people who promote homosexuality, not the public to attack them,” Mr Muhame said.
The newspaper was ordered by the Ugandan High Court to stop publishing the details of homosexuals on privacy grounds but only after 29 people, including Mr Kato, had been “outed”.
Ugandan President Yoweri Museveni at independence day celebrations last year
The growing persecution of homosexuals in Uganda was highlighted in October 2009 when a bill was tabled in the country’s parliament proposing the death penalty for “repeat offenders”.
The legislation prompted an international outcry and was denounced as “odious” by US President Barack Obama.
The bill was shelved but gay rights campaigners fear it may be re-introduced if President Yoweri Museveni is re-elected for a fourth term next month.
Human Rights Watch has called for an investigation into David Kato’s murder and urged the government to protect gays from violence and “hate speech” that could incite it.