On May 17, 2004, the first day that same-gender marriage ceremonies could be legally performed in the Commonwealth, Mayor Menino, a supporter of same-sex marriage, personally welcomed homosexual and lesbian couples to Boston City Hall amid much fanfare and media attention.

From 1996 to 1998, Mayor Menino lobbied the Massachusetts Legislature to pass a home rule petition which would allow the Boston City Council to enact a domestic partners ordinance. In August, 1998, when Acting Governor A. Paul Cellucci vetoed the measure, Mayor Menino, against the advice of his own corporation counsel, arbitrarily and unlawfully instituted a domestic partners benefits program for municipal employees by executive order. This order was challenged in Suffolk County Superior Court by the American Center for Law and Justice and the Catholic Action League of Massachusetts. On July 8, 1999, the Supreme Judicial Court of the Commonwealth, in a unanimous decision written by then-Associate Justice Margaret Marshall, overturned the executive order in Connors vs. the City of Boston.

Since 1994, Mayor Menino has boycotted Boston’s Saint Patrick’s Day Parade because the organizers, the South Boston Allied War Veterans Council, have refused to allow a militant homosexual group, including participants in the infamous 1990 condom throwing incident at Holy Cross Cathedral, to march in the parade. Mayor Menino has also in the past forbidden Boston Police officers, firefighters, and emergency medical technicians from marching in the parade, describing it as "a discriminatory event."

In June of each year, Mayor Menino leads Boston’s Gay Pride Parade, welcomes marchers to Boston, and allows Boston Police officers, in uniform, to march in the parade.

In 2001, Mayor Menino’s Fire Commissioner, Paul Christian, ordered the Boston Fire Department to remove all shamrocks and other expressions of Irish-Catholic identity from Boston fire apparatus, deriding them as "symbols of tribalism."

Each year in June, Mayor Menino allows the pink triangle homosexual flag to be flown over Boston City Hall Plaza as part of Gay Pride celebrations, often personally participating in the flag raising ceremony.

Each year during Gay Pride Week, Mayor Menino sponsors a gay prom for teenagers at Boston City Hall, where condoms have been distributed.

In January 1994, Thomas Menino became the first Boston Mayor to appoint the members of the Boston School Committee. Among his initial appointees was Dr. Elizabeth Reilinger, President and Chief Executive Officer of Crittenton Hastings House, then a major Massachusetts abortuary, which performed over 4000 abortions per year. Since 1998, Dr. Reilinger has been the Chairwoman of the School Committee. Another original appointee by Mayor Menino was the pro-abortion left-wing activist Felix Arroyo, now a member of the Boston City Council.

In March 1994, in its first significant order of public business, Mayor Menino’s appointed School Committee instituted a condom distribution program in the Boston Public Schools.

Under Mayor Menino’s appointed School Committee, the Boston School Department has embraced such homosexual programs as the Safe School Initiative and Gay/Straight Alliances, which teach that homosexual relationships ought to be affirmed. During this same period, the School Department reprimanded and eventually terminated former Boston Latin School teacher Owen O’Malley, a Catholic critic of homosexual ideology.

Mayor Menino is a supporter of needle exchange programs.

Mayor Menino declared June 3, 2005 to be Queer Eye Day in the City of Boston.

Mayor Menino is a supporter of both gay rights and transgendered rights, whereby sexual orientation and identity are included in the protected categories of civil rights legislation. In 2002, Mayor Menino signed into law a City Council ordinance which would force homeowners, including Catholics with children, to rent apartments in their homes to transvestites and persons who have surgically mutilated themselves through so-called sex change operations.

Mayor Menino has maintained at public expense a gay and lesbian liaison office at Boston City Hall.

In 2005, Mayor Menino castigated th Archdiocese of Boston for the closing of Our Lady of Presentation School in Brighton, calling the actions of the Archdiocese "unconscionable" and "reprehensible." Mayor Menino went on to hold a sham graduation cermeony for Our Lady of Presentation students at Faneuil Hall.

Mayor Menino is a longstanding opponent of tuition tax credits and publicly funded tuition vouchers for the parents of Catholic school students.

Mayor Menino’s spouse, Mrs. Angela Menino, has publicly criticized the Catholic Church, telling The Boston Globe that she opposes what she describes as the Church’s "unjust treatment of women."