The Memory Alpha project had its beginnings in September 2003, when Harry Doddema suggested the idea of adapting the very successful structure and organization of Wikipedia for the creation of an open-source Star Trek database. In the past, most Trek reference sites had been run by individuals or small groups, or were massive, unwieldy, difficult to search, and run by closed organizations (such as the official Star Trek website's database).
At the same time, Dan Carlson had been approaching the same problem from the opposite angle. Dan had slowly been building a personal Star Trek database, called Starfleet Reference Databank, for nearly ten years. However, it was still far from complete because of continuing limitations – a database still far from completion. Dan was ultimately facing the fact that creating a truly useful Star Trek database required more time and effort than any one person could reasonably contribute.
The project first began on 11 November 2003, when Harry and Dan started setting up the Memory Alpha software. It was decided that for the sake of simplicity, an existing wiki engine would be used rather than spend time creating one from scratch. Originally, Memory Alpha used TikiWiki as the wiki engine, but after about a week of development, it was decided that the software was too slow and unwieldy for the project's needs. The existing database content (still in its infant stages) was transferred to the MediaWiki engine, which was much more streamlined and oriented towards pure wiki content. In addition, MediaWiki had several features of wiki management that TikiWiki did not, mainly in the realm of text formatting and article organization.
Memory Alpha was officially announced on 5 December 2003, following a brief beta-testing period. The membership gradually grew over the next several weeks, and first gained the spotlight when the project was mentioned by TrekToday on December 23rd.
On 23 March 2004, Memory Alpha suffered a major setback when the database was accidentally deleted during an upgrade of the MediaWiki software. A backup of the database was fortunately available, but that backup was already six weeks out of date. That problem, however, did not stop the Archivists from picking up the pieces and forging ahead, to make Memory Alpha even better than before.
Memory Alpha finally got its own domain name and server account in early April 2004, having previously been hosted on a subdomain of Dan's website, Star Trek Minutiae. The hosting account was provided by Erik Moeller, one of the primary developers of the MediaWiki software. The move gave Memory Alpha the opportunity to grow much larger than before, and also eliminated the problems related to poor service provided by the previous host.
In February 2005, Memory Alpha switched hosting servers and joined Fandom (formerly Wikia, formerly WikiCities), a free, for-profit wiki-hosting company started by Wikipedia founder Jimbo Wales and Wikimedia Foundation board member Angela Beesley.
The expansion of Memory Alpha has continued since April 2004 with the addition of multilingual editions. The Dutch edition was founded on 10 April 2004, and the German edition followed soon after on 14 May 2004. The family now includes a Swedish version (May 2005), a French version (November 2005), an Esperanto version and a Polish version (both February 2006), a Spanish version (3 April 2006), a Serbian version (December 2006), a Czech version and a Russian version (both 17 January 2007), a Portuguese version (20 February 2007), a Chinese version (30 March 2007), a Japanese version (18 January 2008), a Bulgarian version (1 August 2008), an Italian version (25 September 2008), a Catalan version (25 June 2010), a Romanian version (11 May 2015), and a Ukranian version (17 February 2017).
- For more information on starting a version in a new language, see Start a new edition in another language.
On 13 June 2007, Memory Alpha reached another major milestone with the creation of the 25,000th article; the 50,000th article was created on 12 November 2020, nearly seventeen years to the day since its inception.
In 2015, Memory Alpha was credited by Simon Pegg as having been "so helpful" with the writing of Star Trek Beyond.  In 2016, Pegg gave another interview in which he talked highly of the website, noting, "We had the entirety of Star Trek history at our disposal, and it's always there online." After describing Memory Alpha as "amazing", he recalled, "It became Doug [Jung]'s and my resource, and the place that we'd turn to whenever we wanted to know, 'What kind of weapons does an NX vessel carry?' Memory Alpha has it."  Pegg additionally clarified, "We used Memory Alpha extensively to fact-check stuff. I'm pretty knowledgeable of Star Trek, but Memory Alpha has everything, like I don't know exactly what's inside a photon torpedo, or how it's put together, or even much about Vulcan physiognomy, or, you know, the inaugural voyage of the first warp four ship. All that is on Memory Alpha." During the writing of Star Trek Beyond, Pegg also consulted, via email, Harry Doddema and Dan Carlson about naming the Vulcan mineral Vokaya. 
The writing staff of Star Trek: Discovery regularly uses Memory Alpha, which the showrunners of that series regard as "an amazing resource." However, they are also vigilant about doing their own fact-checking of information presented on the wiki. 
Memory Alpha currently hosts 50,871 articles that are being worked on.