Rothblatt contributed $258,000 to SpacePAC, a super PAC that supported her son, Gabriel, who was running as a Democrat in Florida's 8th congressional district but lost. Gabriel is a pastor for the Terasem Movement.

Rothblatt was born in Chicago, Illinois in 1954 to Rosa Lee and Hal Rothblatt, a dentist. She was raised in a suburb of San Diego, California.

As an undergraduate, she became a convert to Gerard K. O'Neill's "High Frontier" plan for space colonization after analyzing his 1974 Physics Today cover story on the concept as a project for Professor Harland Epps' Topics in Modern Astronomy seminar. Rothblatt subsequently became an active member of the L5 Society and its Southern California affiliate, Organization for the Advancement of Space Industrialization and Settlement (OASIS).

Upon graduating from UCLA in 1981 with a joint MBA/JD degree, Rothblatt was hired by the Washington, D.C., law firm of Covington & Burling to represent the television broadcasting industry before the Federal Communications Commission in the areas of direct broadcast satellites and spread spectrum communication. In 1982, she left to study astronomy at the University of Maryland, College Park, but was soon retained by NASA to obtain FCC approval for the IEEE C band system on its tracking and data relay satellites and by the National Academy of Sciences' Committee on Radio Frequencies to safeguard before the FCC radio astronomy quiet bands used for deep space research. Later that year she was also retained as Vice President by Gerard K. O'Neill to handle Business and regulatory matters for his newly invented satellite navigation Technology, known as the Geostar System.

In 1982, Rothblatt married Bina Aspen, a realtor from Compton, California. They have four children together. Rothblatt and Aspen legally adopted each other's children.

Rothblatt is responsible for launching several communications satellite companies, including the first private international spacecom project (PanAmSat, 1984), the first global satellite radio network (WorldSpace, 1990), and the first non-geostationary satellite-to-car broadcasting system (Sirius Satellite Radio, 1990). Rothblatt helped pioneer airship internet services with her Sky Station project in 1997, together with Alexander Haig. She then successfully led the effort to get the US Federal Communications Commission (FCC) to allocate frequencies for airship-based internet services.

In 1994, at age 40, she came out as transgender and changed her name to Martine Aliana Rothblatt. She has since become a vocal advocate for transgender rights.

As an attorney-entrepreneur, Rothblatt was also responsible for leading the efforts to obtain worldwide approval, via new international treaties, of satellite orbit/spectrum allocations for space-based navigation services (1987) and for direct-to-person satellite radio transmissions (1992). She also led the International Bar Association's biopolitical project to develop a draft Universal Declaration on the Human Genome and Human Rights for the United Nations (whose final version was adopted by the UNESCO on November 11, 1997, and endorsed by the United Nations General Assembly on December 9, 1998).

In 2004, Rothblatt launched the Terasem Movement, a transhumanist school of thought focused on promoting joy, diversity, and the prospect of technological immortality via mind uploading and geoethical nanotechnology. Through a charitable foundation, Leaders of this school convene publicly accessible symposia, publish explanatory analyses, conduct demonstration projects, issue grants, and encourage public awareness and adherence to Terasem values and goals. The movement maintains a "Terasem Island" on the Internet-based virtual world Second Life, which is currently composed of two sims, which was constructed by the E-Spaces company.

In a January 4, 2008 blog post titled Marketing Transhumanism, Lawyer and bioethicist Wesley J. Smith ridiculed the feasibility of the Terasem Movement Foundation's claims to offer a free Service that can "preserve one's individual consciousness so that it remains viable for possible uploading with consciousness software into a cellular regenerated or bionanotechnological body by Future Medicine and technology". Smith facetiously questioned whether this offer would be followed by the sale of "longevity products".

In an August 16, 2009 blog post titled The "Imagination" of a Robot Cultist, rhetorician and technocritic Dale Carrico harshly criticized Rothblatt's writings for promoting what he argues to be the pseudoscience of mind uploading and the techno-utopianism of the Californian Ideology. In a February 28, 2010 blog post titled More Serious Futurology from Transhumanist Martine Rothblatt, Carrico criticized Rothblatt's claims about digital Technology and "mindclones" as being nothing more than wishful thinking. In a June 5, 2010 blog post titled Rothblatt's Artificial Imbecillence, Carrico criticized Rothblatt for caring more about rights of "virtual, uploaded persons"—who he argues are neither real nor possible—more than the rights of actual human persons and some nonhuman persons, such as great apes and dolphins.

In a July 4, 2010 New York Times article titled Making Friends with a Robot Named Bina48, Journalist Amy Harmon described as frustrating but occasionally thrilling her conversation with one of "humanity's first cybernetic companions," BINA48, created by Rothblatt and Hanson Robotics. She concluded it was "not that different from interviewing certain flesh and blood subjects."

In September 2016, the world's first electric-powered full-size helicopter took FLIGHT at Los Alamitos Army Airfield. This historic FLIGHT was conceived and mathematically demonstrated by Martine Rothblatt, President of Lung Biotechnology PBC, specified and implemented by Glen Dromgoole of Tier 1 Engineering and piloted by Ric Webb of OC Helicopters. The helicopter, a modified Robinson R44 weighed 2500 pounds with its test pilot, flew for five minutes, attained 400 feet and exceeded 80 knots airspeed, all completely powered by rechargeable batteries. Design and development partners in the project include Rinehart Motion Systems and Brammo, Inc.. The project which was sponsored by Lung Biotechnology PBC is the first phase in the development and production of an Electrically-Powered Semi-Autonomous Rotorcraft for Organ Delivery (EPSAROD). Lung Biotechnology PBC intends to apply the EPSAROD Technology to distributing manufactured organs for transplantation to major hospitals with much less noise and carbon footprint than current Technology.

In September 2017 Forbes Magazine named Rothblatt as one of the 100 Greatest Living Business Minds of the past 100 years. Special reference was made to her roles as a "perpetual reinventor, founder of Sirius and United Therapeutics, and creator of PanAmSat."

In January 2018 Rothblatt was presented the UCLA Medal, the university’s highest award, in recognition of her creation of Sirius XM satellite radio, advancing organ transplant Technology, and having “expanded the way we understand fundamental concepts ranging from communication to gender to the nature of consciousness and mortality.”