The causes of segmentation of mid-ocean ridges by long-lived transform boundaries are poorly understood. Large (>200 km) offsets of the Mid-Atlantic Ridge are distributed neither regularly nor randomly, but are mostly clustered in the equatorial region, where they can be traced outside the active transform to South American and African sheared continental margins. This permanent cluster of transforms is located above a long-lived upper mantle thermal minimum. Permanent transforms at 50°–55°N and perhaps at 45°–50°S are associated with mantle secondary thermal minima. A cluster of transforms disrupts the mid-ocean ridge above a mantle thermal minimum at the Australian-Antarctic discordance. Conversely, “hot” stretches of the Mid-Atlantic Ridge are devoid of major transforms. Low magmatic budget and high-strength rheology of cold, thick lithosphere above cold mantle caused the formation of weak and unstable oceanic rift segments during the opening of the equatorial Atlantic and Australian-Antarctic oceans, favoring the development of initial transform clusters and maintaining them as permanent structural and/or geochemical boundaries. Thus, some long-lived transform clusters may be caused ultimately by upper mantle thermal minima, and not vice versa; thermal anomalies created in the mantle by these transforms (“transform cold edge effect”) are second-order “rebound” effects.